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One of the hallmark features of posttraumatic stress disorder (PTSD) is the re-experiencing of the trauma by flashbacks, spontaneous recollections, and recurrent nightmares of the trauma, which affect over 90% of patients. As such, disrupted trauma memory processing has been proposed as a core factor underlying PTSD symptomatology. Yet, the underlying neurobiological substrate for this is currently unknown.
Bart Dirven, PhD candidate in the research group of Marloes Henckens (department of Cognitive Neuroscience), used a mouse model for PTSD to investigate how trauma memory processing can result in long-term behavioral alterations as a consequence of trauma exposure in mice. Critically, for this, he dissociated mice that showed full recovery from the trauma and remained healthy versus those that lastingly displayed alterations in behavior that resemble symptoms seen in PTSD patients (for example high arousal and vigilance and disrupted sleep). These inter-individual differences as observed in mice mimic the human situation in which most of the trauma-exposed individuals actually recover from trauma exposure and stay healthy. The researchers hypothesized that trauma susceptible mice stored the trauma memory different from resilient ones. Dirven used transgenic mice that enabled him to fluorescently mark the neurons that were active during trauma memory formation. Then, he behaviorally tested the mice on a variety of PTSD-like symptoms and determined which mice were resilient and susceptible. Finally, he re-exposed the mice to the spatial context in which the mice were earlier exposed to the traumatic event to induce trauma memory recall, and assessed the neurons that were activated by staining the mouse brains for activity markers.
Dirven focused in his analyses on the hippocampus, a brain region that is critically involved in memory formation. He observed that trauma susceptible mice did not show deviations during the initial formation of the trauma memory, but that they displayed lower overall activity in certain hippocampal regions during trauma memory recall, as well as altered activity of certain GABAergic (inhibitory) interneurons. Moreover, he observed differences in the expression of epigenetic regulators of neuronal activity (DNA methylation, hydroxymethylation and histone deacetylase 2 expression levels) in the hippocampus of susceptible mice.
These findings, published in Neuroscience, provide initial evidence for aberrant trauma memory storage in trauma susceptible individuals. The work is currently followed up in further studies in the research group of Marloes Henckens, that investigate potential consequences for trauma memory quality as well as the causal role of these memory deviations in the development of PTSD-like symptomatology in mice.
Figure: Mouse brain section showing the hippocampus. Cells in red indicate neurons that were active during trauma memory formation, cells in green indicate neurons that were active during trauma memory recall, and cells in blue indicate parvalbumin neurons, a specific class of GABAergic interneurons.
Read the publication here:
Dirven BCJ, van Melis L, Daneva T, Dillen L, Homberg JR, Kozicz T, Henckens MJAG. Hippocampal Trauma Memory Processing Conveying Susceptibility to Traumatic Stress. Neuroscience. 2024 Jan 12:S0306-4522(24)00015-0. doi: 10.1016/j.neuroscience.2024.01.007. Online ahead of print.
